The primary objective of this proposal is to assess genetic and environmental influences on experimentation with tobacco, alcohol, marijuana, and other drugs using a longitudinal adoption design. This study builds on more than 20 years of data collected as part of the Colorado Adoption Project (CAP), and focuses on the transmission of substance use and antecedent behaviors such as conduct disorder symptoms, other behavioral problems, and academic achievement difficulties. Close integration of measures collected as part of two other components from this center application, Component 2 (Adolescent Substance Abuse), and Component 4 (Adolescent Twins), will facilitate cross-component analysis of substance use and related behavioral problems. Combined analysis of data from this component and component 2 will explicitly test the hypothesis that familial transmission parameters for severe substance abuse and for experimentation in adolescence are distinct. Combined analysis of data from this component and component 4 will test the importance of a specific twin shared environmental parameter that includes cohort effects. By the end of the grant cycle, substance experimentation histories through age 17 will have been obtained from more than 200 adopted probands and 100 genetically unrelated older siblings and 200 matched control early adulthood. In addition, 90 younger siblings of each type will have been followed longitudinally at least to age 15. Some information on substance use by the biological and rearing parents of the probands is currently available; additional information on substance use by rearing parents of the adopted and control probands will be collected. Information on temperament, personality, cognitive abilities, achievement, and adjustment, as well as individual perceptions of the family environment, is available for all CAP participants. Multivariate genetic analyses of combined data sets will also be used to test hypotheses concerning genetic and environmental mediation of the association between behavioral problems, substance experimentation, and achievement.